AstraZeneca Reports “Disappointing” Results From MYSTIC Lung Cancer Trial

Durvalumab / tremelimumab combo fails to improve PFS compared to chemotherapy

The immunotherapy combination of durvalumab (Imfinzi) and tremelimumab did not improve progression-free survival (PFS) compared with platinum-based chemotherapy in previously untreated patients with metastatic non–small-cell lung cancer (NSCLC) in the phase 3 MYSTIC trial.

AstraZeneca announced PFS results for the randomized, open-label, multicenter, global trial of durvalumab monotherapy or durvalumab in combination with tremelimumab versus platinum-based standard-of-care chemotherapy in patients with stage IV, first-line NSCLC whose tumors express programmed death ligand-1 (PD-L1) on 25% or more of their cancer cells. Improving PFS versus chemotherapy was one of the study’s primary endpoints. As a secondary endpoint, although not formally tested, durvalumab monotherapy would not have met a prespecified threshold of PFS benefit over standard of care in this disease setting.

The trial will continue to assess two additional primary endpoints of overall survival (OS) for durvalumab monotherapy and OS for the durvalumab plus tremelimumab combination. Final OS data from both primary endpoints are expected during the first half of 2018.

 “While the results from the MYSTIC trial for progression-free survival in first-line stage IV non–small-cell-lung cancer compared with standard of care are disappointing, the trial was designed to assess overall survival and we look forward to evaluating the remaining primary endpoints of overall survival for both mono- and combination therapy,” said Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca.

AstraZeneca recently received accelerated approval from the FDA for durvalumab in previously treated patients with locally advanced or metastatic urothelial carcinoma.

Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor's immune-evading tactics and inducing an immune response. Tremelimumab is an investigational human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 and blocks its activity, contributing to T-cell activation and boosting the immune response to cancer.

Source: AstraZeneca; July 27, 2017.